Competition between antigen-specific T cells for peptide:MHC (p:MHC) complexes shapes the ensuing T cell response. Mouse model studies provided compelling evidence that competition is a highly effective mechanism controlling the activation of naïve T cells. However, assessing the effect of T cell competition in the context of a human infection requires defined pathogen kinetics and trackable naïve and memory T cell populations of defined specificity. A unique cohort of non-myeloablative hematopoietic stem cell transplant (nmHSCT) patients allowed us to assess T cell competition in response to CMV reactivation, which was documented with detailed virology data. In our cohort, HSCT donors and recipients were CMV-seronegative and -positive, respectively, thus providing genetically distinct memory and naïve T cell populations. We used single-cell transcriptomics to track donor versus recipient-derived T cell clones over the course of 90 days. We found that donor-derived T cell clones proliferated and expanded substantially following CMV-reactivation. However, for immunodominant CMV epitopes, recipient-derived memory T cells remained the overall dominant population. This dominance was maintained despite more robust clonal expansion of donor-derived T cells in response to CMV reactivation. Interestingly, the donor-derived T cells that were recruited into these immunodominant memory populations shared strikingly similar TCR properties with the recipient-derived memory T cells. This selective recruitment of identical and nearly identical clones from the naïve into the immunodominant memory T cell pool suggests that competition does not interfere with rejuvenating a memory T cell population, but results in selection of convergent clones to the memory T cell pool.

中文翻译：

---

造血干细胞移植患者供体和受体来源的 CMV 特异性 T 细胞的趋同克隆选择

抗原特异性 T 细胞之间对肽：MHC (p:MHC) 复合物的竞争形成了随后的 T 细胞反应。小鼠模型研究提供了令人信服的证据，证明竞争是控制幼稚 T 细胞活化的高效机制。然而，在人类感染的背景下评估 T 细胞竞争的影响需要明确的病原体动力学和可追踪的具有明确特异性的初始和记忆 T 细胞群。一组独特的非清髓性造血干细胞移植 (nmHSCT) 患者使我们能够评估 T 细胞对 CMV 再激活的反应，并记录了详细的病毒学数据。在我们的队列中，HSCT 供体和受体分别为 CMV 血清阴性和阳性，因此提供了遗传上不同的记忆和初始 T 细胞群。我们使用单细胞转录组学在 90 天内跟踪供体与受体衍生的 T 细胞克隆。我们发现供体来源的 T 细胞克隆在 CMV 再激活后大量增殖和扩增。然而，对于免疫优势 CMV 表位，受体来源的记忆 T 细胞仍然是总体优势群体。尽管响应 CMV 再激活，供体来源的 T 细胞的克隆扩增更加强劲，但这种优势仍然存在。有趣的是，被招募到这些免疫显性记忆群中的供体来源的 T 细胞与受体来源的记忆 T 细胞具有惊人相似的 TCR 特性。